Familial Nephropathy, FN

 

Gene: COL4A4

Transmission: Autosomal, recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Cocker Spaniel mutation: Substitution, COL4A4 gene; c.115A>T; p.(K39 STOP), exon3

Springer Spaniel mutation: Substitution, COL4A4 gene; c.2712 C>T, p.(Q905 Stop), exon30

Medical system: Renal

Breeds: American Cocker Spaniel, English Cocker Spaniel, English Springer Spaniel, Labrador Retriever, Welsh Springer Spaniel

Age of onset of symptoms: Around the age of 5 months with a urine test. The clinical signs appear between 6 months and 2 years.

Familial nephropathy of the English Springer Spaniel is a fatal genetic disease that affects the basement membrane of glomeruli thus impairing kidney function.  In normal conditions, proteins are not present in the urine, but in double mutant affected dogs an excessive amount of protein is found in the urine.  Animals develop clinical signs of chronic renal failure such as marked loss of appetite, vomiting, weight loss and weakness and have polydipsia (excessive drinking) and polyuria (excessive urination).  In general, affected animals die during the year following the appearance of the first clinical signs.

 

References:

OMIA links: [0710-9615] , [2618-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Andrade LR, Caceres, AM, Trecenti AS, et al. (2020) Allele frequency of nonsense mutation responsible for hereditary nephropathy in English cocker spaniel dogs. Vet Anim Sci 9:100114.  [pubmed/32734115]

Lees GE. (2013) Kidney diseases caused by glomerular basement membrane type IV collagen defects in dogs.  J Vet Emerg Crit Care (San Antonio) 23(2):184-93.  [pubmed/23464675]

Nowend KL, Starr-Moss AN, Lees GE, Berridge BR, et al. (2012) Characterization of the genetic basis for autosomal recessive hereditary nephropathy in the English Springer Spaniel. J Vet Intern Med 26:294-301. [pubmed/22369189]